The management of hemostasis (control of bleeding) is an important requirement for a successful surgery. The exposure of blood to foreign surfaces, which often occurs during surgery, as well as the surgery itself, can induce the activation of the clotting factors.
The clotting mechanism can be mediated in a variety of ways. One of the more common methods of preventing coagulation is to administer heparin.
The administration of heparin, however, must be done carefully. Care is required because the response of any one patient to a particular dose of heparin is highly variable, depending upon the particular physiology of each patient. Thus, it is often quite necessary for physicians or other caregivers to understand the response of a patient such that a proper heparin dosage may be administered.
The Medtronic Hepcon® Hemostasis Management System Plus (HMS Plus) may be used to measure many blood parameters, including activated clotting time (ACT). The Medtronic Hepcon® HMS Plus system uses the ACT to base the Heparin Dose Response cartridge to measure individual response to heparin in vitro. The heparin dose response curve may be seen in FIG. 1.
The heparin dose response requires a small sample of whole blood from a patient. The whole blood is introduced into particular assay channels or vials, at least one (and preferably two) of the assay cartridge having no heparin reagent, at least one (and preferably two) more assay channels having a heparin reagent concentration of A and at least one (and preferably two) more assay channels having a heparin reagent concentration of B, where the concentration denoted as A is different from the concentration denoted as B.
The test begins by introducing the same volume of blood into each of the channels or vials. Thereafter the blood is mixed (preferably using a plunger.) The blood clots in each of the channels or vials at differing times. The clot is measured by timing the descent rate of the plunger. Ultimately, the clotting of each of the vials or channels may be graphed as shown in FIG. 1, where line 1 may be drawn through the three data points created by the time taken for blood to clot in each channel or vial. That is, blood without any heparin (depicted here as data point DPO), blood with heparin reagent concentration A (depicted here as data point DPA) and blood with heparin reagent concentration B (depicted here as data point DPB). As seen, the heparin dose response is a linear function when the ACT is used to initiate coagulation.
The heparin dose response line varies from patient to patient. That is, the linear heparin dose response seen in FIG. 1 has different slopes for different individuals. Patients may have a heparin dose response line having slopes such as those seen as line 1′ (very low slope) or line 1″ (very high slope.) Generally speaking, the flatter or lower the slope of the line the more heparin resistant the patient is. Heparin resistant patients may have different reasons accounting for the heparin resistance. For example, these patients may have mechanisms which complex or bind the heparin, not allowing the heparin to inhibit blood coagulation. There may also be mechanisms present in the patient that rapidly eliminate the heparin. Finally, these patients may be heparin resistant due to low levels of the serine protease inhibitor antithrombin III (AT III). Heparin is a catalyst, that is, it helps prevent coagulation by accelerating the natural anticoagulant mechanisms present in the patient. The primary mechanism is the inhibition of thrombin, the primary protease of blood coagulation, by AT III. Without adequate amounts of AT III, heparin is ineffective in preventing blood coagulation.
AT III targets proteases of the coagulation cascade, and in particular thrombin. Heparin accelerates the rate with which AT III inhibits the proteases. Thus, without the presence of AT III, the anticoagulant activity of heparin is severely diminished. The differences in which individuals respond to heparin may be affected by the differences in their AT III levels. Thus, a goal of the present system is to provide a method of reliably assessing the heparin dose response while further accessing whether such heparin dose response is attributable to presence or absence of sufficient levels of AT III within the patient and whether the fresh whole blood (and thus patient) has, or requires additional, AT III.
Reference is made to a commonly owned U.S. Pat. No. 6,541,262 and corresponding PCT application WO 01/082793, which are incorporated by reference herein in their entirety. These references disclose a method for assessing the heparin dose response and whether the heparin dose response is attributable to the presence or absence of AT III.
A batch of test cartridges preloaded with reagents can be made in advance of testing a blood sample by means of an HMS Plus-type machine and may be stockpiled at a medical or surgical facility for convenient use during a medical or surgical procedure. Test cartridges are then taken from the stored batch of cartridges, as they may be needed for testing while other test cartridges remain in storage. However, a practical difficulty with stored reagents in the test cartridges is to have assurance that the stored reagents will remain active and will produce consistent, reliable results as the cartridges in the batch age.